Article(id=1307013513831019210, tenantId=1146029695717560320, journalId=1306274286668972124, issueId=1307013423896753139, articleNumber=null, orderNo=null, doi=10.11843/j.issn.0366-6964.2026.03.015, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1750867200000, receivedDateStr=2025-06-26, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1789545904834, onlineDateStr=2026-09-16, pubDate=1774195200000, pubDateStr=2026-03-23, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1789545904834, onlineIssueDateStr=2026-09-16, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1789545904834, creator=13701087609, updateTime=1789545904834, updator=13701087609, issue=Issue{id=1307013423896753139, tenantId=1146029695717560320, journalId=1306274286668972124, year='2026', volume='57', issue='3', pageStart='1177', pageEnd='1776', issueExtLink='null', onlineDate='null', pubDate='1774195200000', pubDateStr='2026-03-23', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=1, specialIssue=null, createTime=1789545883392, creator='13701087609', updateTime=1789609930841, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1307282058464743901, tenantId=1146029695717560320, journalId=1306274286668972124, issueId=1307013423896753139, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1307282058464743902, tenantId=1146029695717560320, journalId=1306274286668972124, issueId=1307013423896753139, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=1334, endPage=1347, ext={EN=ArticleExt(id=1307013515429049035, articleId=1307013513831019210, tenantId=1146029695717560320, journalId=1306274286668972124, language=EN, title=Impact of Co-infecting Factors on Pathogenicity of Porcine Epidemic Diarrhea Virus, columnId=1307007397399126026, journalTitle=Acta Veterinaria et Zootechnica Sinica, columnName=REVIEW, runingTitle=null, highlight=null, articleAbstract=

Porcine epidemic diarrhea virus (PEDV) is a major pathogen causing diarrhea in piglets and has led to significant economic losses in the global swine industry since its emergence. In practice, co-infection with multiple pathogens is commonly observed alongside PEDV, complicating its prevention and control. These co-infecting factors mainly include various viruses, bacteria, parasites, and toxins, which can exacerbate clinical symptoms in infected pigs. This review systematically summarizes the factors commonly co-infecting with PEDV and their impact on its pathogenicity. The results show that porcine kobuvirus (PKV), porcine Sapelovirus (PSV), porcine deltacoronavirus (PDCoV), porcine rotavirus (PRoV) and transmissible gastroenteritis virus (TGEV) are the most common porcine diarrheal viruses co-infecting with PEDV, with PKV and PSV representing emerging trends in recent years. Among bacteria, Escherichia coli, C. perfringens, and C. difficile are frequently detected in co-infections with PEDV. Additionally, parasites such as Entamoeba spp. and various toxins have also been confirmed to co-infect with PEDV. In terms of pathogenicity, PEDV co-infection can exacerbate clinical symptoms, increase PEDV load in the intestine, cause more severe intestinal barrier damage, and trigger a stronger immune response in pigs. These findings lay a foundation for future studies on the mechanisms of PEDV co-infection. Moreover, this review analyzes current prevention and control strategies and identifies existing limitations, aiming to raise awareness of PEDV co-infection among the livestock industries and to promote the implementation of scientific and sustainable control measures, thereby supporting healthier pig production, and improving overall farming efficiency.

, authors=Yingying GUO1, 2, 3, Ke YUE1, 2, 3, Xing ZHANG1, 2, 3, Qiuying YU2, 3, 4, Kunmiao HE1, 2, 3, Jiajia YIN1, 2, 3, Na WANG1, 2, 3, 4, Gaiping ZHANG1, 2, 3, authorsList=Yingying GUO, Ke YUE, Xing ZHANG, Qiuying YU, Kunmiao HE, Jiajia YIN, Na WANG, Gaiping ZHANG, authorCompany=null, correspAuthors=Na WANG, authorNote=null, correspAuthorsNote=
WANG Na, E-mail:
, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1307013521871499994, articleId=1307013513831019210, tenantId=1146029695717560320, journalId=1306274286668972124, language=CN, title=共感染因素对猪流行性腹泻病毒致病性的影响, columnId=1307007397566898188, journalTitle=畜牧兽医学报, columnName=综述, runingTitle=null, highlight=null, articleAbstract=

猪流行性腹泻病毒(PEDV)是引起仔猪腹泻的重要病原,自流行以来一直严重损害全球养殖业发展。生产中常存在多种病原体与PEDV的混合感染,导致其防治困难,这些共感染因素主要涉及各类病毒、细菌、寄生虫和毒素等,并引起猪产生更为严重的临床症状。为此,本文系统梳理了临床上常与PEDV发生共感染的因素及其对PEDV致病性的影响。结果表明,猪嵴病毒(PKV)、猪萨佩罗病毒(PSV)、猪丁型冠状病毒(PDCoV)、猪轮状病毒(PRoV)和猪传染性胃肠炎病毒(TGEV)是最常与PEDV发生共感染的猪腹泻病毒,其中PKV和PSV正成为近年来新型混合感染趋势;大肠杆菌、产气荚膜梭菌和艰难梭菌是常与PEDV发生混合感染的细菌。猪阿米巴虫等寄生虫以及多种毒素亦被证实可与PEDV共同感染。在致病性方面,PEDV共感染可导致猪临床症状加重、肠道中PEDV载量升高、肠道屏障破坏更为显著以及更强烈的免疫反应,这些发现为PEDV混合感染机制的研究奠定了基础。此外,本文进一步分析了当前PEDV共感染防治策略的现状与存在的不足,以期引起养殖场对PEDV共感染问题的重视,推动科学、绿色防控措施的实施,从而促进猪群健康养殖,提升养殖效益。

, authors=郭颖莹1, 2, 3, 岳珂1, 2, 3, 张兴1, 2, 3, 余秋颖2, 3, 4, 何坤淼1, 2, 3, 殷佳佳1, 2, 3, 王娜1, 2, 3, 4, 张改平1, 2, 3, authorsList=郭颖莹, 岳珂, 张兴, 余秋颖, 何坤淼, 殷佳佳, 王娜, 张改平, authorCompany=null, correspAuthors=王娜, authorNote=

郭颖莹,硕士生,主要从事预防兽医学研究,E-mail:

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王娜,主要从事食品安全与免疫研究,E-mail:
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A. Ranking of average co-detection rates of PEDV with other porcine diarrhea viruses; B. Annual trends of the top three PEDV co-infection types

, figureFileSmall=71IB6oBwZKC8SUJRr2jo2A==, figureFileBig=20YCZAekB+gDIdPAk9rShw==, tableContent=null), ArticleFig(id=1307281681484895157, tenantId=1146029695717560320, journalId=1306274286668972124, articleId=1307013513831019210, language=CN, label=图2, caption=PEDV与其他猪腹泻病毒混合感染特征及其时间分布

A. PEDV与其他猪腹泻病毒平均混合检出率排名;B. 前3名混合感染类型随年份变化趋势

, figureFileSmall=71IB6oBwZKC8SUJRr2jo2A==, figureFileBig=20YCZAekB+gDIdPAk9rShw==, tableContent=null), ArticleFig(id=1307281681543615414, tenantId=1146029695717560320, journalId=1306274286668972124, articleId=1307013513831019210, language=EN, label=Fig.3, caption=PEDV co-infection exacerbates clinical symptoms

A. Body weight difference between co-infection groups and PEDV group; B. Fecal scores of co-infection groups

, figureFileSmall=79ztGV2dyyh2XEanfWPWRw==, figureFileBig=/cNlmILsQnH56DqhToJ/PA==, tableContent=null), ArticleFig(id=1307281681598141367, tenantId=1146029695717560320, journalId=1306274286668972124, articleId=1307013513831019210, language=CN, label=图3, caption=PEDV共感染加重临床症状

A.混合感染组与PEDV组体重差值;B.混合感染组粪便得分情况

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A. Changes in intestinal PEDV load in co-infection groups compared to the PEDV group; B. Changes in fecal PEDV levels in co-infection groups compared to the PEDV group

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A.混合感染组相比PEDV组肠道内PEDV载量变化;B.混合感染组相比PEDV组粪便中PEDV含量变化

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共感染因素对猪流行性腹泻病毒致病性的影响
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郭颖莹 1, 2, 3 , 岳珂 1, 2, 3 , 张兴 1, 2, 3 , 余秋颖 2, 3, 4 , 何坤淼 1, 2, 3 , 殷佳佳 1, 2, 3 , 王娜 1, 2, 3, 4 , 张改平 1, 2, 3
畜牧兽医学报 | 综述 2026,57(3): 1334-1347
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畜牧兽医学报 |综述 2026 , 57 (3) : 1334 -1347
共感染因素对猪流行性腹泻病毒致病性的影响
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郭颖莹1, 2, 3 , 岳珂1, 2, 3, 张兴1, 2, 3, 余秋颖2, 3, 4, 何坤淼1, 2, 3, 殷佳佳1, 2, 3, 王娜1, 2, 3, 4 , 张改平1, 2, 3
作者信息
  • 1.河南农业大学动物医学院,郑州 450046
  • 2.动物免疫学国际联合研究中心,郑州 450046
  • 3.龙湖现代免疫实验室,郑州 450046
  • 4.河南农业大学食品科学技术学院/郑州市营养与健康食品重点实验室,郑州 450002
通讯作者:
王娜,主要从事食品安全与免疫研究,E-mail:
作者简介:

郭颖莹,硕士生,主要从事预防兽医学研究,E-mail:

Impact of Co-infecting Factors on Pathogenicity of Porcine Epidemic Diarrhea Virus
Yingying GUO1, 2, 3 , Ke YUE1, 2, 3, Xing ZHANG1, 2, 3, Qiuying YU2, 3, 4, Kunmiao HE1, 2, 3, Jiajia YIN1, 2, 3, Na WANG1, 2, 3, 4 , Gaiping ZHANG1, 2, 3
Affiliations
  • 1.College of Veterinary Medicine,Henan Agricultural University,Zhengzhou 450046,China
  • 2.International Joint Research Center of National Animal Immunology,Zhengzhou 450046,China
  • 3.Longhu Laboratory,Zhengzhou 450046,China
  • 4.College of Food Science and Technology,Henan Agricultural University/Zhengzhou Key Laboratory of Nutrition and Health Food,Zhengzhou 450002,China
  • Corresponding Author:
    WANG Na, E-mail:
出版时间: 2026-03-23 doi: 10.11843/j.issn.0366-6964.2026.03.015
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猪流行性腹泻病毒(PEDV)是引起仔猪腹泻的重要病原,自流行以来一直严重损害全球养殖业发展。生产中常存在多种病原体与PEDV的混合感染,导致其防治困难,这些共感染因素主要涉及各类病毒、细菌、寄生虫和毒素等,并引起猪产生更为严重的临床症状。为此,本文系统梳理了临床上常与PEDV发生共感染的因素及其对PEDV致病性的影响。结果表明,猪嵴病毒(PKV)、猪萨佩罗病毒(PSV)、猪丁型冠状病毒(PDCoV)、猪轮状病毒(PRoV)和猪传染性胃肠炎病毒(TGEV)是最常与PEDV发生共感染的猪腹泻病毒,其中PKV和PSV正成为近年来新型混合感染趋势;大肠杆菌、产气荚膜梭菌和艰难梭菌是常与PEDV发生混合感染的细菌。猪阿米巴虫等寄生虫以及多种毒素亦被证实可与PEDV共同感染。在致病性方面,PEDV共感染可导致猪临床症状加重、肠道中PEDV载量升高、肠道屏障破坏更为显著以及更强烈的免疫反应,这些发现为PEDV混合感染机制的研究奠定了基础。此外,本文进一步分析了当前PEDV共感染防治策略的现状与存在的不足,以期引起养殖场对PEDV共感染问题的重视,推动科学、绿色防控措施的实施,从而促进猪群健康养殖,提升养殖效益。

猪流行性腹泻病毒  /  共感染  /  致病性  /  防治现状

Porcine epidemic diarrhea virus (PEDV) is a major pathogen causing diarrhea in piglets and has led to significant economic losses in the global swine industry since its emergence. In practice, co-infection with multiple pathogens is commonly observed alongside PEDV, complicating its prevention and control. These co-infecting factors mainly include various viruses, bacteria, parasites, and toxins, which can exacerbate clinical symptoms in infected pigs. This review systematically summarizes the factors commonly co-infecting with PEDV and their impact on its pathogenicity. The results show that porcine kobuvirus (PKV), porcine Sapelovirus (PSV), porcine deltacoronavirus (PDCoV), porcine rotavirus (PRoV) and transmissible gastroenteritis virus (TGEV) are the most common porcine diarrheal viruses co-infecting with PEDV, with PKV and PSV representing emerging trends in recent years. Among bacteria, Escherichia coli, C. perfringens, and C. difficile are frequently detected in co-infections with PEDV. Additionally, parasites such as Entamoeba spp. and various toxins have also been confirmed to co-infect with PEDV. In terms of pathogenicity, PEDV co-infection can exacerbate clinical symptoms, increase PEDV load in the intestine, cause more severe intestinal barrier damage, and trigger a stronger immune response in pigs. These findings lay a foundation for future studies on the mechanisms of PEDV co-infection. Moreover, this review analyzes current prevention and control strategies and identifies existing limitations, aiming to raise awareness of PEDV co-infection among the livestock industries and to promote the implementation of scientific and sustainable control measures, thereby supporting healthier pig production, and improving overall farming efficiency.

porcine epidemic diarrhea virus  /  co-infection  /  pathogenicity  /  prevention and control status
郭颖莹, 岳珂, 张兴, 余秋颖, 何坤淼, 殷佳佳, 王娜, 张改平. 共感染因素对猪流行性腹泻病毒致病性的影响. 畜牧兽医学报, 2026 , 57 (3) : 1334 -1347 . DOI: 10.11843/j.issn.0366-6964.2026.03.015
Yingying GUO, Ke YUE, Xing ZHANG, Qiuying YU, Kunmiao HE, Jiajia YIN, Na WANG, Gaiping ZHANG. Impact of Co-infecting Factors on Pathogenicity of Porcine Epidemic Diarrhea Virus[J]. Acta Veterinaria et Zootechnica Sinica, 2026 , 57 (3) : 1334 -1347 . DOI: 10.11843/j.issn.0366-6964.2026.03.015
在养殖业中,猪流行性腹泻病毒(PEDV)作为一种具有高度传染性的冠状病毒,自首次发现以来一直在全球范围内广泛传播,持续给全球养殖业的经济带来巨大的损失[1]。PEDV作为一种引发猪肠道疾病的病原体,主要临床症状包括腹泻、呕吐和脱水等,并且尤其对哺乳仔猪具有极高的致病性,常伴随着90%以上的死亡率[2]。在2025年5月,中国Ⅱ类动物疫病报告结果中显示,PEDV引起的发病数和病死数仍位居榜首[3]。PEDV引起的流行不仅直接导致养殖场猪的大量死亡,还极大增加了养殖厂的饲养管理成本和疫病控制的难度,并且对全球猪肉产业链构成了巨大的威胁。
多年来,研究者们围绕PEDV的致病机制、药物阻断方法及疫苗开发已开展了大量研究,并取得了显著进展[4⁃6]。然而,PEDV的防控依然面临挑战,特别是在实际生产环境中,猪群往往暴露于多种病原体的混合感染之下[7]。PEDV共感染现象在实际生产中的发生非常普遍,尤其是在大型养殖场中,猪群同时感染猪圆环病毒[8](PCV)、猪繁殖与呼吸综合征病毒[9](PRRSV)等病原体的情况屡见不鲜。这些共感染因素极可能进一步增强PEDV的致病性,加重猪临床症状,引起猪病情复杂化,并且可能干扰机体对药物和疫苗的应答反应,从而显著增加疾病防控难度,并造成更大的经济损失。
这些共感染因素极可能进一步增强PEDV的致病性,加重猪的临床症状,进而削弱药物和疫苗的防护效果,从而显著增加疾病防控难度,并造成更大的经济损失。
为此,本综述旨在系统性地梳理临床上常与PEDV发生共感染的因素以及它们对PEDV致病性的影响,为抗PEDV药物和疫苗的开发及养殖场防控管理方法提供理论依据,并为其他猪群传染病的综合防治提供重要参考。
猪在全球农业市场中占据重要地位,是主要的肉类来源之一[2]。流行病学调查表明,PEDV常与多种病原体共存于实际生产环境中,形成复杂的感染网络[10⁃12]。
PEDV与多种病毒的混合感染在猪群中时有发生[13-14]。这些病毒的混合感染可发生在不同科、属、种及毒株之间。2004—2024年的流行性病学调查显示,猪群中PEDV的阳性检出率总体平均约为39.23%,在19.29%~51.16%波动。阳性率自2010年起逐步上升,并于2020年达到峰值,之后呈下降趋势[15⁃19](图1)。多种病毒的平均混合检出率约为32.60%[14,19⁃21]。在与PEDV混合感染的病毒中,猪腹泻病毒最为常见,主要包括猪丁型冠状病毒(PDCoV)、猪传染性胃肠炎病毒(TGEV)、猪急性腹泻综合征病毒(SADS-CoV)、猪轮状病毒(PRoV)、猪萨佩罗病毒(PSV)、猪嵴病毒(PKV)以及猪博卡病毒(PBoV)等[18-19,22⁃24]。这类病毒的临床表现通常均为腹泻、呕吐和脱水等,并且在病理特征上具有很高的相似性,难以直接通过临床症状进行鉴别[22]。据调查统计,PEDV与猪腹泻病毒的混合感染在临床上很是常见(图2)。其中,以PKV、PSV、PDCoV、PRoV和TGEV与PEDV的平均混合检出率较高,分别为15.79%、9.03%、3.14%、2.24%和1.24%(图2A)。进一步分析发现,PKV和PSV与PEDV的混合检出率在2015年后所占比重高于PDCoV,成为新型混合感染趋势(图2B)。其次,PCV[18,25⁃28]、PRRSV[9]和牛病毒性腹泻病毒(BVDV)[29]也是PEDV常见的另几种共感染病毒。调查显示,PCV与PEDV的平均混合检出率约为27.37%[18,25⁃28]。Zhao等[30]研究表明,PEDV与PRRSV的混合检出率可达33.30%。相比之下,BVDV最初仅感染牛,但后续研究发现其亦可感染猪。Cheng等[29]对2017—2020年采集自中国的1 078份粪便样本进行检测,发现PEDV阳性样本中BVDV的共检率达17.24%。调查显示,BVDV的跨物种传播可能通过与邻近牛场的直接接触、气溶胶传播、感染妊娠母猪后的垂直传播,以及人员、车辆、器械的机械携带或受污染疫苗、血清制品的使用等多种途径实现[31]。这种跨物种传播不仅可能增加病毒间的遗传变异风险,还可能对动物群体健康和公共安全构成更大威胁。此外,众多调查显示,PEDV与两种以上病毒的混合感染在猪群中同样频发,腹泻仔猪粪便样品平均可检测出5.5种不同的病毒[32]。因此,PEDV与其他病毒的共感染在临床极为常见,这无疑对猪场的防控提出了更大的挑战。
病原传播具有复杂性,PEDV同样常与一些细菌发生共感染,进一步增加治疗和防控的难度。调查显示,大肠杆菌(Escherichia coli)、产气荚膜梭菌(C. perfringens)和艰难梭菌(C. difficile)是PEDV常见的共感染细菌。在单一共感染方面,Lee、Mertens和Mesonero-Escuredo等分别对采集的临床样本检测后发现,PEDV与大肠杆菌的共检出率几乎接近100%[11, 33];与产气荚膜梭菌的共检出率分别为14.78%(30/203)[34]和1.8%(2/109)[11],其中,A型产气荚膜梭菌(C. perfringens type A,CPA)占据主导地位;与艰难梭菌的共检出率为3.0%(5/166)[35]。此外,进一步调查发现,PEDV还可与肠道沙门菌(Salmonella enterica)发生共感染,其共检出率为2.89%(5/173)[36]。
除单一共感染外,PEDV与多种细菌的多重共感染在实际生产中亦较常见。例如,PEDV与大肠杆菌及产气荚膜梭菌的三重共检出率为0.92%(1/109)[11],与艰难梭菌及产气荚膜梭菌的混合检出率为1.2%(2/166)[35],与肠道沙门菌及大肠杆菌的混合检出率为1.16%(2/173)[36]。此外,一些衣原体早期也在腹泻猪体内被鉴定,提示PEDV亦可能与衣原体等其他细菌发生共感染或继发感染,但相关研究尚不充分,亟需进一步调查[37]。
除病毒与细菌外,寄生虫与PEDV的共感染亦是影响猪群健康的重要因素。临床调查显示,猪鞭毛虫、球虫、弓形虫、隐孢子虫和阿米巴虫等常在猪腹泻病例中被检出[38-39]。在日本206头腹泻猪体内发现,猪阿米巴虫检出率达25.7%[40];对采自中国青藏高原藏猪的100份粪便样品进行检测,发现隐孢子虫、毕氏肠微孢子虫和芽囊原虫检出率分别为8.3%、56.7和50.0%[41]。这些结果表明,猪寄生虫的感染非常普遍。然而,目前关于PEDV与寄生虫的共感染研究仍相对匮乏,仅在部分报道中发现PEDV与大肠纤毛虫(Neobalantidium coli)、芽囊原虫(Blastocystis)、溶组织内阿米巴(Entamoeba histolytica)、布特氏四毛滴虫(Tetratrichomonas buttreyi)和猪三毛滴虫(Tritrichomonas suis)的共检出[12]。寄生虫感染可引起慢性炎症和营养吸收障碍,降低猪的生长速度与养殖效益,有关其与PEDV共感染的系统研究仍需进一步加强[42]。
在猪群饲养过程中,因环境污染、饲料加工不当等管理疏漏,猪常暴露于多种毒素,包括细菌毒素、真菌毒素、动物毒素和植物毒素等。这些毒素可通过饲料、水源或空气进入体内,并与PEDV产生协同致病效应。例如,猪A型产气荚膜梭菌产生的内毒素和外毒素具有肠道毒性,可加剧肠黏膜损伤,并通过上调DC-SIGN(树突状细胞特异性细胞间黏附分子-3-结合非整合素分子)表达和增强PEDV S蛋白棕榈酰化,促进病毒感染[43]。真菌毒素(如呕吐毒素、黄曲霉毒素)则能破坏肠道屏障、扰乱肠道微生态平衡、抑制免疫细胞活性,增加宿主对PEDV的易感性[44-45];动物毒素如蜂毒、蛇毒和蝎毒具有神经、肠道或血液等毒性,在与PEDV并存时可直接或间接削弱猪肠道和免疫防御能力,引发血管损伤与应激反应,为PEDV复制创造有利条件[46]。此外,植物毒素如氰苷类、毒芹碱等也可通过饲料摄入,干扰猪正常生理功能,进一步增强PEDV的致病性[47]。因此,毒素在猪群饲养中的影响亦不容忽视,应采取有效管理措施,减少猪的毒素摄入,以降低其与PEDV的协同致病风险。
近年来,一些学者针对其他病原体对PEDV致病性影响开展了大量研究,并取得了显著成果。研究结果显示,PEDV与其他病原体的共感染往往会引起PEDV致病性发生改变,具体表现如下。
PEDV感染的典型临床表现为不同程度的呕吐、腹泻和脱水[2]。在共感染条件下,许多共感染病原体自身亦可引发类似症状,从而加重或改变PEDV感染猪的临床表现[22]。首先,在猪存活率与精神状态方面,PEDV与其他病原体的共感染可导致感染猪存活率进一步下降,厌食、呕吐和脱水等症状的加剧[8,48]。例如,在PEDV与PRoV共感染研究中,共感染组猪的死亡率(80.88%)相比于PEDV单独感染组(59.09%)则显著升高[49]。在PEDV与PKV共感染试验中,共感染组相比于PEDV组的呕吐、脱水和厌食情况显著加重[50]。其次,在体重变化方面,共感染组猪体重相比于PEDV组出现明显下降,如PEDV与PRoV、PDCoV或CPA共感染组体重下降分别达4.48、2.29和0.54 kg(图3A)[9,34,51]。此外,在腹泻程度方面,共感染组猪只表现为腹泻情况的加重,持续时间的延长以及恢复时间的延后(图3B)。Zhang等[51]针对PEDV与PDCoV共感染情况开展研究后发现,PEDV单独感染组在第4天(dpi)仅出现轻度腹泻,在6 dpi即恢复。而PEDV和PDCoV共感染组在2 dpi即出现水样腹泻,并且一直持续至14 dpi,直至16 dpi腹泻情况才有所恢复。类似结果在PEDV分别与CPA[34]和PRoV[49]的研究中同样被证实。
与健康猪相比,PEDV感染猪常伴随着肠道组织内PEDV的广泛定植和复制,以及粪便中病毒粒子的持续排出[6]。既往研究表明,PEDV可感染肠道的各个部位,其中以空肠中部和回肠为主要侵袭区,并且具有较高的病毒载量[52]。在PEDV共感染研究中,目前已发现其他病原体的存在可影响PEDV在肠道内的复制水平。研究表明,PEDV共感染可引起肠道内PEDV载量显著升高(图4A)。Wu等[50]观察发现,PEDV与PKV的共感染可显著提高小肠内的PEDV载量,并且以空肠增加量最为显著。类似地,在PEDV与PRoV、PCV和PDCoV共感染模型中,同样观察到共感染组肠道内PEDV载量的升高[49]。然而,这些研究显示,尽管共感染引起PEDV病毒载量增加,但均未改变肠道内PEDV的组织嗜性,仍以空肠和回肠绒毛上皮细胞为主要定殖点。此外,粪便中PEDV病毒粒子的排出情况亦可作为评估肠道内PEDV感染情况的间接指标(图4B)。研究发现,PEDV与CPA共感染时,共感染组的病毒脱落量显著高于单独感染组[34]。这一现象同样在PEDV与PRoV[49]以及PDCoV[53]的共感染中观察到。
PEDV作为一种典型的肠道病毒,主要侵袭肠道上皮细胞,破坏肠道屏障结构,影响肠道健康与功能[54]。在共感染条件下,PEDV与其他病原体协同作用,加重这一破坏过程,导致肠道健康状况进一步变差。在肠道物理屏障方面,大体病理学结果表明,PEDV与其他病原体共感染时,猪表现出更为严重的肠道扩张,中度至重度肠道膨胀,且肠道出血现象更加明显,并伴随更大量未消化的粘液状黄色凝乳[34,48,50⁃51]。组织病理学观察进一步表明,共感染猪只肠绒毛萎缩程度加剧,上皮细胞坏死脱落比例明显升高,肠上皮刷状缘结构更加不规则,以及绒隐比(绒毛高度/隐窝深度,反映肠道损伤程度)(图5)的进一步下降,且尤以空肠区域的变化最为显著[44,49⁃50,53,55]。此外,在共感染组中,紧密连接蛋白如Claudin-1、Occludin和ZO-1的表达水平亦观察到显著下降[56]。在化学屏障方面,共感染组常表现为肠道杯状细胞数量的改变,MUC2等主要黏蛋白表达水平的下降,刷状缘内消化酶活性与数量的减少,以及黏液层变薄,从而引起肠道通透性增加,病原体更易接触并穿透肠上皮造成更严重的损伤[53,55,57]。在生物屏障方面,PEDV与其他病原体的混合感染可引起肠道菌群紊乱。Shu[58]等研究发现,PEDV与PDCoV共感染显著改变了猪肠道菌群结构。在门水平,放线菌门(Actinobacteria)的数量显著增加;在科水平,拟杆菌科(Bacteroidaceae)、韦荣氏球菌科(Veillonellaceae)和红蝽菌科(Coriobacteriaceae)的丰度显著上升,瘤胃球菌科(Ruminococcaceae)显著下降;在属水平,拟杆菌(Bacteroides),光谱拟杆菌(Mitsuokella)和科林斯菌(Collinsella)的数量也显著增多。这些菌群数量的改变通常与肠道炎症反应的发生和屏障功能的受损密切相关[59-60]。因此,PEDV与其他病原体的共感染可通过破坏肠道物理结构、干扰化学屏障分泌及扰乱肠道微生态平衡,显著削弱肠道屏障功能,从而进一步引起肠道损伤加剧。
PEDV感染后可显著影响猪的免疫系统,一方面通过激活先天免疫反应,如上调TLR和RLR等模式识别受体的表达,以增强机体对病毒的清除能力;另一方面则抑制机体免疫功能,尤其通过干扰Ⅰ型干扰素(IFN)的产生,促使病毒逃避免疫识别与清除,从而实现免疫逃逸[61]。研究表明,PEDV与其他病原体共感染的情境下,这些免疫反应将发生更复杂和剧烈的变化,主要体现在以下三个方面:(1)先天免疫系统更早、更强烈地激活。在PEDV与PDCoV、BVDV或TGEV共感染后,一些参与天然免疫应答相关的基因(如TLR、RIG-I、MDA5等模式识别受体)均表现出显著上调。特别是在感染早期,共感染组中TLR家族表达水平相比于PEDV单独感染组出现显著升高,并且在早期更显著的诱导TRAF6介导的NF-κB信号通路的激活以及Ⅰ型IFN的应答,从而增强早期的抗病毒反应[29,57,62]。(2)先天免疫细胞数量的上升。共感染可导致先天免疫细胞在肠道组织中的积聚增加。Liang等[57]研究表明,PEDV与PDCoV共感染后,十二指肠和空肠中CD3⁺ T淋巴细胞和B淋巴细胞的数量显著上升,提示黏膜先天免疫系统激活程度的增强。(3)细胞因子表达上升。共感染引发的宿主体内免疫反应的增强将进一步通过免疫级联反应促使大量细胞因子的产生和释放。一些促炎细胞因子和免疫调节因子的表达水平出现显著升高。在PEDV与PDCoV或BVDV共感染模型中,促炎细胞因子如TNF-α、IL-6、IL-8和IL-18的表达显著升高,一些免疫调节因子(如IL-10、IL-22、IL-23、IL-33)与PEDV单独感染组相比进一步释放[51,53,57,62]。这些细胞因子的大量释放,一方面可以增强机体抗病毒效应,有助于病原体的清除,但另一方面其过度表达亦可能导致病毒免疫耐受的形成,加重肠道组织损伤,从而促进病毒的免疫逃逸,并增加临床症状的严重程度。
PEDV传染性强,致死率高,全球养殖业每年因其造成的经济损失可达9亿~18亿美元,而养殖场内共感染因素的存在无疑将进一步加剧经济损失。针对PEDV共感染的防治,目前主要涉及以下几方面。
物理方法,主要是指利用各种物理手段(如高温、干燥、紫外照射或机械冲洗)对潜在的各类病原体实现隔离与灭活。例如,可采用高温灭菌、热风干燥或高压水冲等方式,对饲料、饮水系统、养殖设备及猪舍环境进行处理,从而降低环境中病原微生物的存活与传播风险。作为养殖管理中的基础性措施,物理防控在共感染防治中发挥着不可或缺的作用,但这种方法只能提供一定程度的防护效果。对于养殖户的日常管理,应同步强化生物安全管理体系建设。新引入猪(如后备母猪)应设置2~4周的隔离观察期,通过临床评估与病原检测排除潜在带毒风险,降低各类病原群体传播概率。严格对饲养环境进行日常清洁与周期性高压冲洗,尤其是对猪舍、饲喂设备及运输车辆等高频接触物体表面,结合物理灭菌处理,进一步降低环境中各类病原载量[63⁃64]。构建以“零引入、零残留”为目标的闭环生物安全管理体系,严格落实人员进出流程、交叉污染区域分区管理等制度。此外,应积极构建早期智能预警与快速检测体系,通过全场联网智能监控系统、“分群监测”机制、图像识别算法及联动式智能耳标或项圈等技术手段,实现病猪或异常圈舍的精准定位与即时隔离,有效提升养殖场对PEDV共感染的响应速度与应急处置能力[65-66]。
化学方法,主要是通过应用消毒剂等化学物质抑制或灭活病毒、细菌、寄生虫和毒素等,从而降低它们在养殖环境与饲料中的传播风险,提升生物安全水平。在实际防控中,常采用过氧化氢、水合过氧化物及超氧化水等作为有效的环境消毒剂。例如,研究表明,在常温条件下,使用超氧化水处理10~90 min即可有效灭活病原[67];而在金属(如运输车厢)表面污染环境中,过氧化氢及其衍生消毒剂在20 ℃下作用30 min或在-10~4 ℃条件下作用10~30 min,均可达到良好的灭活效果[68]。对于畜舍内粪便的消毒,使用加速型过氧化氢(AHP)类消毒剂(如0.5%维康-S或2.06%高乐氏漂白液)处理猪粪,可显著降低其中病原体RNA的检出水平,有效抑制病原体传播[69]。此外,考虑到许多病原体可以通过口腔传播,因此动物饲料的消毒同样至关重要,常采用湿法消毒处理方式。研究证实,通过将饲料加热至130 ℃以上,或采用高剂量电子束辐照(≥50 kGy),均可有效降低病原体RNA含量,抑制它们在饲料中的增殖活性[70]。与此同时,考虑到病原体联合与耐受的形成,应在使用消毒剂时选择具有广谱效能的联合型消毒剂并周期性轮换使用,避免耐受病原的形成。然而,物理和化学方法因作用时间短、覆盖范围有限,且防护效果易受环境条件与操作规范影响等,其防控效能存在一定局限性。
疫苗免疫仍是控制PEDV及其共感染病原的核心防控策略,主要包括常规疫苗和新型疫苗两大类。目前,常规疫苗中多联灭活疫苗(如TGEV-PEDV〔CV777 GI-a〕、TGEV-PEDV〔GII-b〕疫苗[71-72])具有良好的安全性与成熟的生产工艺,但灭活疫苗存在保护起效时间相对较长且免疫持续时间较短、需借助有效佐剂等问题,尤其是对于一些基础免疫不好的初产母猪,在未及时产生具有保护作用的分泌型IgA(sIgA)的情况下,可能导致哺乳仔猪感染风险升高。因此,应根据猪群生理阶段和免疫状态,合理制定免疫程序,如妊娠母猪可在妊娠中后期(如孕90和110 d)分别接种经验证的多价灭活疫苗或与安全性良好的活疫苗联合使用,提升母源抗体水平,实现仔猪早期保护。对于哺乳仔猪,应鼓励其在出生2 h内充分摄取初乳,并考虑补充乳铁蛋白、β-葡聚糖等免疫调节剂,以确保被动免疫成功[73]。对于断奶仔猪,应结合母源抗体水平下降时间,合理安排PEDV、PRRSV、PCV等疫苗接种,避免发生免疫干扰,从而实现更高效的免疫保护效果。多联活疫苗(如TGEV-PEDV、rTGEV-RS-SPEDV、TGEV-PEDV-RV),具有较强的免疫原性,能更有效的诱导宿主免疫反应[74⁃75]。然而,其保护效果在面对突变迅速的流行毒株时仍存在一定局限性。因此,新型疫苗的设计和开发孕育而生。这类疫苗主要包括核酸疫苗、基因工程亚单位疫苗、病毒样颗粒疫苗和活载体疫苗,具有靶向性强、安全性高、能够系统性诱导宿主体液免疫、细胞免疫及黏膜免疫等多层次免疫应答的优势[76]。近年来,如针对PEDV S与TGEV S和PoRV VP7基因融合开发的DNA疫苗、PEDV-PDCoV-MHV三价病毒样颗粒疫苗以及rPRRSV-PEDV病毒载体活疫苗均相继开发[77⁃79]。然而,这类新型疫苗在商业化应用中仍面临诸多技术瓶颈,包括抗原表达系统不稳定、冷链储运依赖性强、生产成本高和剂型安全性评估周期长等。此外,规模化免疫推广尚缺乏统一标准和评估体系,进一步制约其临床转化效率。
在PEDV及其共感染的综合防控中,药物干预作为疫苗免疫与物理化学防控手段的有效补充,发挥着重要作用。当前主要策略包括抗体药物、核苷酸类抗病毒药物、抗生素、干扰素及植物源药物等[80]。抗体类药物如sIgA和IgY(卵黄免疫球蛋白)在降低仔猪腹泻率和病毒排毒方面表现良好,尤其IgY作为饲料添加剂,适用于哺乳仔猪群体,但其疗效易受个体差异、病程进展和吸收效率影响,临床应用仍需优化[81⁃82]。核苷酸类药物如GC376蛋白酶抑制剂和莫努匹韦可阻断病毒蛋白酶活性或干扰RNA合成,展现出良好的抗病毒作用。但此类药物起效相对缓慢,需联合免疫调节剂或改善递送系统以提高稳定性和靶向性[83⁃84]。干扰素作为天然免疫因子,能够诱导抗病毒蛋白表达并调节炎症反应,在抑制PEDV等病毒感染方面具有显著效果[85]。在PEDV与细菌共感染情况下,抗生素如雷帕霉素、格瑞菲新等具有抗菌作用同时还表现出一定的抗病毒作用[86⁃88]。然而,大量广谱抗生素的使用可能加剧细菌耐药性并破坏宿主肠道微生态平衡[89]。随着养殖业中“禁抗”政策的推行,传统依赖抗生素控制细菌共感染的策略正面临转型压力,开发替代性防治手段势在必行。
植物源性药物因其多靶点、低毒性和生态友好等特点,正成为PEDV共感染综合防治的重要方向。其主要指从天然植物中提取得到的具有药理活性的成分,如黄酮、多酚、生物碱等,具有广谱抗病毒、抗菌、抗寄生虫和抗毒素等作用。例如,槲皮素、番茄碱和25-羟基胆固醇等已被证实对PEDV、TGEV和PDCoV等多种猪肠道冠状病毒具有广谱抑制作用[90]。多酚类,如姜黄素,不仅具有抗PEDV和PRRSV等病毒的能力,还能有效抑制大肠杆菌和沙门菌等致病菌的增殖,同时可缓解毒素诱导的氧化应激反应[91⁃92]。在PEDV共感染和“禁抗”政策背景下,植物源性药物展现出良好的综合防治潜力。然而,目前,有关植物活性成分在猪体内的药代动力学特性研究较为薄弱,体内代谢效率、剂量-效应关系、生物利用度以及作用机制的系统验证尚不充分,限制了其在规模化养殖中的精准应用与剂量优化。同时,针对PEDV共感染的联合用药研发尚不系统全面。因此,未来应进一步加强相应药代动力学特性研究,借助人工智能技术(如中医药智能平台(ITCM)平台)加速推进新型联合防治药物的开发,并不断优化活性成分的提取与纯化工艺,以及探索纳米中药、发酵中药等新型制剂形式,助力其在PEDV共感染综合防治中的转化应用[93⁃94]。
本文系统梳理与综述了实际生产中常与PEDV发生共感染的因素及其对PEDV致病性的影响。尽管现有研究在该方面已取得一定进展,但仍存在许多亟待解决的问题。首先,现有关于PEDV共感染的筛查仍缺乏系统性和全面性,研究多聚焦于PEDV与其它病毒的共感染,而对细菌、寄生虫等关注较少。其次,针对不同病原与PEDV混合感染模式的临床研究仍相对匮乏,混合感染背景下各病原的致病优势尚不明确。同时,混合感染下对猪致病性的具体调控机制有待深入阐明。多数研究结果显示PEDV共感染可显著加重猪疾病严重程度。然而,存在研究表明,在相同混合感染模型下亦表现出差异不显著的现象。例如,以研究较多的PEDV+PDCoV混合感染模型为例,在Saeng-chuto等[53]、Shu等[58]和Zhang等[51]的独立研究中均表明,与PEDV单独感染组相比,PEDV+PDCoV同时感染可显著加重猪腹泻程度,增加大体及组织病理学损伤,升高粪便中PEDV含量和肠道病毒载量,降低肠道肠绒隐比,并诱导更强烈的炎性因子表达反应。而在Jung等[95]的研究中显示,同样是在PEDV+PDCoV同时感染条件下,与PEDV单独感染组相比,混合感染组腹泻程度、粪便中PEDV含量、肠道内PEDV病毒载量和肠道肠绒隐比均无显著差异。这一现象的产生原因可能与研究使用的毒株型号、感染剂量不同等因素相关,其背后的调控机制仍需更系统的研究加以阐释。此外,目前关于PEDV共感染时空流行特征分析仍较为匮乏,当前研究多集中于共感染病原的阳性检出率情况,缺乏不同季节、养殖阶段以及养殖模式等变量对PEDV共感染影响的动态评估、系统性调查与数据支撑。与此同时,养殖场内PEDV共感染的防控仍需加强。因此,未来研究可从以下几个方面开展:一是构建更全面的共感染病原筛查谱,利用宏基因组、纳米孔高通量测序等技术,加强PEDV与细菌、寄生虫等非病毒性病原共感染的系统调查。二是深入解析PEDV共感染条件下多病原协同致病的分子机制,系统揭示不同病原组合对PEDV复制、传播及宿主响应的调控途径,并明确各混合感染模式下的优势致病病原;三是加强PEDV共感染的时空特征分析,开展不同季节、养殖阶段及养殖模式下的动态监测与数据采集,探索环境因素、生物安全水平等对共感染发生率的影响。四是在“禁抗”政策背景下,探索以植物源性药物为代表的绿色干预策略,为构建安全、可持续的PEDV共感染防控体系提供理论支持与技术保障。
  • 河南省重大科技专项项目(221100110600)
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2026年第57卷第3期
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doi: 10.11843/j.issn.0366-6964.2026.03.015
  • 接收时间:2025-06-26
  • 首发时间:2026-09-16
  • 出版时间:2026-03-23
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  • 收稿日期:2025-06-26
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河南省重大科技专项项目(221100110600)
作者信息
    1.河南农业大学动物医学院,郑州 450046
    2.动物免疫学国际联合研究中心,郑州 450046
    3.龙湖现代免疫实验室,郑州 450046
    4.河南农业大学食品科学技术学院/郑州市营养与健康食品重点实验室,郑州 450002

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王娜,主要从事食品安全与免疫研究,E-mail:
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2种不同金属材料的力学参数
科
Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)
属
Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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